What began as a curious phenomenon in Drosophila melanogaster over 30 years ago, the so-called heat shock (stress) response now constitutes an active area of research in both cell biology and medicine. The response, characterized by the increased expression of the heat shock (stress) proteins in cells exposed to a variety of environmental insults, represents a basic and universal cellular defense mechanism. Despite their designation, most of the stress proteins are produced at relatively high levels in the normal cell and are essential components of a number of important biological pathways. Examples include the role of the hsp 70 and hsp 60 (GroEL) families of stress proteins in facilitating the proper maturation of other intracellular proteins, and the participation of hsp 90 in the regulation of various protein kinases and transcription factors such as the steroid hormone receptors. Within medicine, changes in stress protein expression are observed during tissue/organ traumas and in various diseased states. Work in our laboratory has focused on the identification and characterization of the stress proteins produced in mammalian cells. Over the next few years we will continue our studies examining the structure/function of the individual stress proteins. In particular, we will: i) complete the purification and characterization of the stress proteins and prepare suitable antibodies to each; ii) examine in detail the properties of the related hsp 90 and grp 94; iii) pursue in detail the role of the hsp 70 family in facilitating protein maturation events and determine how such events are compromised in the cell experiencing stress; iv) determine the consequences of microinjection into living cells the purified stress proteins or their corresponding antibodies; and v) pursue collaborative efforts examining the role of the stress response/proteins in medicine/disease.